Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl and CuSO aqueous solutions on DNA methyl...

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Published inExperimental and therapeutic medicine Vol. 21; no. 1; p. 100
Main Authors Iftode, Andrada, Drăghici, George Andrei, Macașoi, Ioana, Marcovici, Iasmina, Coricovac, Dorina E, Dragoi, Razvan, Tischer, Alina, Kovatsi, Leda, Tsatsakis, Aristidis M, Cretu, Octavian, Dehelean, Cristina
Format Journal Article
LanguageEnglish
Published Greece Spandidos Publications 01.01.2021
Spandidos Publications UK Ltd
D.A. Spandidos
Subjects
Antibiotics
Cadmium
Cancer cells
Cell culture
Colorectal cancer
Copper
Cytotoxicity
Deoxyribonucleic acid
Development and progression
DNA
DNA methylation
Epigenetic inheritance
Epigenetics
Gene expression
Genetic aspects
Health aspects
Methylation
Morphology
Mutation
Pathogenesis
Penicillin
Risk factors
Software
Tumorigenesis
Romania
DNA methylation
cadmium
copper
cytotoxicity
HT-29 cells
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Summary:Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl and CuSO aqueous solutions on DNA methylation in HT-29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti-migratory potential of these substances. The results showed a dose-dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT-29 cell migration capacity. In addition, RT-qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT-29 cells and their capacity to induce epigenetic changes.
Bibliography:Dr Razvan Dragoi, Department of Balneology, Rehabilitation and Rheumatology, Faculty of Medicine, ‘Victor Babes’ University of Medicine and Pharmacy, 2 P-ta Murgu Eftimie, 300041 Timisoara, Romania dragoi.razvan@umft.ro
Abbreviations: AGS, gastric adenocarcinoma cell line; AsPC-1, tumor pancreatic cells; ATCC, American Type Cell Collection; Cd, Cadmium; COX-2, cyclooxygenase-2; Cu, Copper; FBS, fetal bovine serum; FLC-4, hepatoma cell line; HCT116, colon carcinoma cell line; HEK293, embryonic kidney cell line; HPNE, healthy pancreatic cells; HT-29, human colorectal carcinoma cells; IARC, International Agency for Research on Cancer; MAPK, mitogen activated protein kinase; MCF7, breast carcinoma cell line; MDA-MB468, breast carcinoma cell line; PBS, phosphate saline buffer; PGE2, prostaglandin E2; ROS, reactive oxygen species; TE4, esophageal carcinoma cell line
Contributed equally
ISSN:1792-0981
1792-1015
DOI:10.3892/etm.2020.9532